Fenofibrate Decreases Hepatic P-Glycoprotein in a Rat Model of Hereditary Hypertriglyceridemia

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F19%3A73594032" target="_blank" >RIV/61989592:15110/19:73594032 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00023001:_____/19:00077658

Výsledek na webu

<a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373460/pdf/fphar-10-00056.pdf" target="_blank" >https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6373460/pdf/fphar-10-00056.pdf</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2019.00056" target="_blank" >10.3389/fphar.2019.00056</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Fenofibrate Decreases Hepatic P-Glycoprotein in a Rat Model of Hereditary Hypertriglyceridemia

Popis výsledku v původním jazyce

P-glycoprotein (P-gp) is a membrane-bound transporter encoded by Mdr1a/Abcb1a and Mdr1b/Abcb1b genes in rodents involved in the efflux of cytotoxic chemicals and metabolites from cells. Modulation of its activity influences P-gp-mediated drug delivery and drug-drug interaction (DDI). In the current study, we tested the effects of fenofibrate on P-gp mRNA and protein content in non-obese model of metabolic syndrome. Males hereditary hypertriglyceridemic rats (HHTg) were fed standard laboratory diet (STD) (Controls) supplemented with micronized fenofibrate in lower (25 mg/kg b. wt./day) or in higher (100 mg/kg b. wt./day) dose for 4 weeks. Liver was used for the subsequent mRNA and protein content analysis. Fenofibrate in lower dose decreased hepatic Mdr1a by 75% and Mdr1b by 85%, while fenofibrate in higher dose decreased Mdr1a by 90% and Mdr1b by 92%. P-gp protein content in the liver was decreased by 74% in rat treated with fenofibrate at lower dose and by 88% in rats using fenofibrate at higher dose. These findings demonstrate for the first time that fenofibrate decreases both mRNA and protein amount of P-gp and suggest that fenofibrate could affect bioavailability and interaction of drugs used to treat dyslipidemia-induced metabolic disorders.

Název v anglickém jazyce

Fenofibrate Decreases Hepatic P-Glycoprotein in a Rat Model of Hereditary Hypertriglyceridemia

Popis výsledku anglicky

P-glycoprotein (P-gp) is a membrane-bound transporter encoded by Mdr1a/Abcb1a and Mdr1b/Abcb1b genes in rodents involved in the efflux of cytotoxic chemicals and metabolites from cells. Modulation of its activity influences P-gp-mediated drug delivery and drug-drug interaction (DDI). In the current study, we tested the effects of fenofibrate on P-gp mRNA and protein content in non-obese model of metabolic syndrome. Males hereditary hypertriglyceridemic rats (HHTg) were fed standard laboratory diet (STD) (Controls) supplemented with micronized fenofibrate in lower (25 mg/kg b. wt./day) or in higher (100 mg/kg b. wt./day) dose for 4 weeks. Liver was used for the subsequent mRNA and protein content analysis. Fenofibrate in lower dose decreased hepatic Mdr1a by 75% and Mdr1b by 85%, while fenofibrate in higher dose decreased Mdr1a by 90% and Mdr1b by 92%. P-gp protein content in the liver was decreased by 74% in rat treated with fenofibrate at lower dose and by 88% in rats using fenofibrate at higher dose. These findings demonstrate for the first time that fenofibrate decreases both mRNA and protein amount of P-gp and suggest that fenofibrate could affect bioavailability and interaction of drugs used to treat dyslipidemia-induced metabolic disorders.

Druh

J_SC - Článek v periodiku v databázi SCOPUS

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

—

Návaznosti

—

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

—

Svazek periodika

10

Číslo periodika v rámci svazku

56

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

4

Strana od-do

1-4

Kód UT WoS článku

000458056700001

EID výsledku v databázi Scopus

2-s2.0-85065907944